The Forsyth Institute, the world's leader in oral and craniofacial disease research, requests $3.79 million to renovate 8,935 ft2 of space for laboratory, core facility, office and clinical research use to create a new interdisciplinary research center of excellence: the Center for Discovery at the Host -Biofilm Interface (CHBI). This project represents a significant expansion of the Institute's research programs, and builds upon Forsyth's internationally-renowned research programs in microbiology/molecular genetics, microbial informatics and immunology. The stage is now set for new paradigm-setting interdisciplinary center that uses the oral cavity as a model system to focus on a critical question: how do humans co-exist with their microbial passengers? The creation of the CHBI will involve the recruitment of 6-8 new principal investigators who will synergize with our existing research strengths, and will generate dramatic new advances in understanding how humans co-exist with their microbial 'passengers'in health, and how perturbations at the host-biofilm interface lead to disease. An aggressive campaign will recruit new scientists in the following areas: human genetics/genomics and proteomics;salivary biology;microbial-epithelial interactions;ontogeny of the immune system;regulatory mechanisms at mucosal surfaces;establishment of commensalism;microbial-mineralized tissue interactions;and clinical/translational research particularly relating to oral-systemic disease interactions in diabetes, metabolic syndrome, obesity, cardiovascular disease, inflammatory bowel diseases, premature birth, and others. The CHBI will be further integrated as appropriate into the newly funded Harvard-wide CTSC ('CATALYST', http:catalyst.harvard.edu), and the Harvard Center for Systems Biology. The funding at Forsyth that will be impacted by this programmatic expansion is: $11,666,314 (40 active projects), and fifty-five (55) pending projects ($17,194,158). To our knowledge, the CHBI will be unique in the field of oral health, and will allow Forsyth to bring its long leadership in this field to a new level. The background to this application is that Forsyth will be relocating its present operation to a new state-of the art facility in the Kendall Square area of Cambridge MA, in early Summer 2010. The Institute will lease space for a minimum of15 years (with two additional 5 year options), thus guaranteeing long term occupancy of renovated space. Because Forsyth's existing program relocation per se will occur independent of ARRA construction grant funding, this application requests support only for renovation of space for program expansion for the creation of the CHBI. This program expansion is 'shovel ready'and must be completed by early Summer 2010. It will involve substantial U.S. job creation. This includes immediate job impact (construction and equipment manufacture, 15-17 U.S. jobs), and substantially more long term sustainable employment: 6-8 principal scientists and approximately 18-24 technical personnel including post-doctoral fellows and laboratory technicians. Accordingly, 39-49 new U.S. jobs will be created should this application be funded.